Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Huang, J; Das, SK; Jha, P; Al Zoughbi, W; Schauer, S; Claudel, T; Sexl, V; Vesely, P; Birner-Gruenberger, R; Kratky, D; Trauner, M; Hoefler, G.
The PPARα agonist fenofibrate suppresses B-cell lymphoma in mice by modulating lipid metabolism.
Biochim Biophys Acta. 2013; 1831(10):1555-1565 Doi: 10.1016/j.bbalip.2013.04.012 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Leading authors Med Uni Graz

Höfler Gerald

Huang Jianfeng

Co-authors Med Uni Graz

Al-Zoughbi Wael

Birner-Grünberger Ruth

Claudel Thierry

Das Suman Kumar

Kratky Dagmar

Schauer Silvia

Trauner Michael

Vesely Paul

Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Abstract:

Obesity is associated with an increased risk for malignant lymphoma development. We used Bcr/Abl transformed B cells to determine the impact of aggressive lymphoma formation on systemic lipid mobilization and turnover. In wild-type mice, tumor size significantly correlated with depletion of white adipose tissues (WAT), resulting in increased serum free fatty acid (FFA) concentrations which promote B-cell proliferation in vitro. Moreover, B-cell tumor development induced hepatic lipid accumulation due to enhanced hepatic fatty acid (FA) uptake and impaired FA oxidation. Serum triglyceride, FFA, phospholipid and cholesterol levels were significantly elevated. Consistently, serum VLDL/LDL-cholesterol and apolipoprotein B levels were drastically increased. These findings suggest that B-cell tumors trigger systemic lipid mobilization from WAT to the liver and increase VLDL/LDL release from the liver to promote tumor growth. Further support for this concept stems from experiments where we used the peroxisome proliferator-activated receptor α (PPARα) agonist and lipid-lowering drug fenofibrate that significantly suppressed tumor growth independent of angiogenesis and inflammation. In addition to WAT depletion, fenofibrate further stimulated FFA uptake by the liver and restored hepatic FA oxidation capacity, thereby accelerating the clearance of lipids released from WAT. Furthermore, fenofibrate blocked hepatic lipid release induced by the tumors. In contrast, lipid utilization in the tumor tissue itself was not increased by fenofibrate which correlates with extremely low expression levels of PPARα in B-cells. Our data show that fenofibrate associated effects on hepatic lipid metabolism and deprivation of serum lipids are capable to suppress B-cell lymphoma growth which may direct novel treatment strategies. This article is part of a Special Issue entitled Lipid Metabolism in Cancer. Copyright © 2013 The Author. Published by Elsevier B.V. All rights reserved.

Find related publications in this database (using NLM MeSH Indexing)

Animals -

B-Lymphocytes - cytology B-Lymphocytes - drug effects

Cell Proliferation - drug effects

Fatty Acids, Nonesterified - blood

Fenofibrate - pharmacology

Hypolipidemic Agents - pharmacology

Lipid Metabolism - drug effects

Liver - drug effects Liver - metabolism

Lymphoma, B-Cell - metabolism Lymphoma, B-Cell - pathology Lymphoma, B-Cell - prevention & control

Male -

Mice -

Mice, Inbred C57BL -

PPAR alpha - agonists

Find related publications in this database (Keywords)

Cachexia

Lipid metabolism

B-cell lymphoma

Tumor growth

PPAR

Fenofibrate

© Med Uni Graz • Imprint